Abnormal Variations in the Expressions of LRP5, Runx2, Osterix and RANKL in Bone Tissues Associated With Postmenopausal Osteoporotic Fractures
Abstract Objective: To investigate the variations in the expressions of LRP5, Runx2, Osterix, and RANKL factors in bone tissues associated with postmenopausal osteoporotic fractures (PMOPF). Method: Postmenopausal patients with femur fractures were initially divided into control (31 cases) and PMOPF groups (83 cases). All control group patients were operated within 1 day after injury. The patients with PMOPF were operated based on the time after fracture in the respective groups (patients were divided into groups A, B, and C based on the time after fracture). Samples were collected from femurs at fracture sites during the operation. The expression level of each factor in bone tissues was detected using RT-qPCR, and the bone mass samples were decalcified and then histologically analyzed by immunohistochemistry. We subsequently analyzed significant differences in the expressions of factors (LRP5, Runx2, Osterix, and RANKL) between PMOPF and control groups. Results: (1) LRP5, β-catenin, Runx2, and Osterix were under-expressed in patients with PMOPF relative to the controls (P<0.05). In contrast, RANKL was over-expressed in the PMOPF group when compared to the control group (P<0.05); (2) the expressions of LRP5 and Runx2 were lowest in Group A patients (1–3 days after fracture). Osterix expression was lowest in Group C patients (8–14 days after fracture). Conversely, RANKL expression was highest in Group B patients (4–7 days after fracture). Conclusion: The inhibition or reduction in the expressions of osteogenic factors including LRP5, Runx2, and Osterix of the Wnt/β-catenin and BMP-2/Runx2/Osterix signaling pathways are associated with PMOPF incidence. Specifically, upregulation of RANKL in the RANKL/RANK signaling pathway is associated with the incidence of PMOPF. LRP5 and Runx2 expressions decreased considerably within 1-3 days after fracture; Osterix expression decreased considerably within 8-14 days after fracture; RANKL expression was highest within 4-7 days after fracture, which could be associated with bone repair in PMOPF. The expression level of the aforementioned factors affects the development and progression of PMOPF.